Human Polymorphisms Professor Janaki Natalie Parikh

Malaria Anthropologist’s “fave” diseases: Malaria & sickle cell anemia How does one contract malaria? Bite of a mosquito. Will any mosquito do? Mosquitoes of the Genus Anopheles Mosquito is actually a vector (carrier) of something that makes us sick.What?

Malaria Protozoan, specifically Plasmodium falciparum Where is this endemic (widespread problem)? Tropical regions: Central & W. Africa, India, S.E. AsiaC. America Pac.Islands. Northern SouthAmerica

How bad is the problem? (#3 killer in world) htm malaria-discovered-in-rainforests-of-costa-rica/ What can we do? Currently no actual cure avail., prophylactic medicine is (prophylaxis?) Preventive med. Prophylaxisanecdote

Mosquitoes & Breeding Anopheles mosquito breeding requirements Similar to mosquitoes in general? sunwarmed, stagnant (still) water

Sickle Cell Anemia (SCA) A genetically inherited disease that affects the shape of hemoglobin protein What does it mean to be anemic? Shortage of red blood cells (rbc’s) SCA is chronic & specific to hemoglobin: a type of protein that binds oxygen in rbc’s Originated as result of a singlepoint mutationon 1 amino acid

Genetics behind SCA AA: 100% AS: 60% 40% SS: 100% Mosaicism: neither ofthese alleles is truly dominant

Heterozygote advantage Thus a heterozygote does not have the disease but is has “sickle cell trait” (carrier) anemia/DS00324/DSECTION=all&METHOD=print anemia/DS00324/DSECTION=all&METHOD=print If this allele has such lethal potential, why didn’t natural selection“weed it out”? heterozygotes are relatively immune to malaria

Mechanisms for SCA heterozygote advantage Lower incidence of infection, lower frequency of transmission Infected cells slow process if sickled & lysed Sickled cells cause damage to protozoan Infected rbc’s “leak” K rapidly, protozoan requires ample K to reproduce

Ecology of SCA & malaria ~7000 yrs ago, pt. mutation gives rise to sickle allele No reproduct. Advantage conferred, allele is very low levels ~5000 yrs ago, ppl in forested areas of W. & C. Africa began shift to agriculture (requires?) Cutting downtrees This inadvertently encourages?

Ecology of SCA cont’d ↑ mosq. breeding, meaning ↑ in malaria rates S allele still low levels, individuals w/ S allele are spared malaria, creating? Reproductive advantage, natural selection operates on S allele, makingit more abundant in subsequent generations Selection continues until a balanced polymorphism is attained

Balanced Polymorphism Balanced polymorphism: AS x AS AS A S In a malarial environment, this process will continue w/ each generation, bringing about stable allele frequencies, meaning that nearly all adults will be heterozygous AAAS SS

Transient polymorphism In a non-malarial region: AS x AS AS A S Transient polymorphism: loss of one allele over time (it’s level is changing, albeit, extremely slowly) Environment: AAAS SS

Rate of natural selection on alleles Deleterious dominants & recessives exist, however, deleterious dominants are weeded out rather quickly Ex: Achondroplastic dwarfism, inhibits growth in long bones of a individual, coded for by a mutated dominant allele: A, a AA = death Aa = a. dwarfism aa = “normal (unaffected)

Late onset deleterious dominant Huntington’s chorea: H, h Genotypes: HH: death Hh: Huntington’s chorea hh: unaffected Doesn’t set in until an individ. is in their 40s or 50s thus natural selection cannot operate on this trait, why? Post reproductive yrs. Remember, natural selection operates through reproduction! Other late onset diseases?

Deleterious recessive Degenerative nerve disorder, Tay-Sach’s disease: T, t TT: unaffected Tt: unaffected, carrier tt: Tay-Sach’s disease Heterozygote advantage exists in this case as well Check out “Curse & Blessing of the Ghetto” article for details

Summary/Myths Traits do not emerge due to heterozyg. advantage, but advantage may make existing trait more common SCA is not a racial, nor an African disease Natural selection cannot operate quickly/efficiently upon recessive alleles since they are hidden/masked Natural selection cannot operate upon late onset diseases since they do not impact reproduction N.S. solutions are far from ideal, but rather, messy solutions due to random nature